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Pulmonary drug delivery

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https://www.readbyqxmd.com/read/28645838/sensitivity-analysis-and-uncertainty-quantification-in-pulmonary-drug-delivery-of-orally-inhaled-pharmaceuticals
#1
Jun Lu, Jinxiang Xi, Joseph E Langenderfer
In spite of widespread use of modeling tools in inhalation dosimetry, it remains difficult to quantify the output uncertainties when subjected to various sources of input variability. This study aimed to develop a computational model that can quantify the input sensitivity and output uncertainty in pulmonary drug delivery by coupling probabilistic analysis package NESSUS with ANSYS Fluent. An image-based mouth-lung model was used to simulate the transport and deposition of drug particles and variability in particle size, density, and inhalation speed were considered...
June 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28629803/development-of-mpc-dpa-polymeric-nanoparticle-systems-for-inhalation-drug-delivery-applications
#2
Abdul Khaliq Elzhry Elyafi, Guy Standen, Steven T Meikle, Andrew L Lewis, Jonathan P Salvage
Inhalation of nanoparticles for pulmonary drug delivery offers the potential to harness nanomedicine formulations of emerging therapeutics, such as curcumin, for treatment of lung cancer. Biocompatible nanoparticles composed of poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) have been shown to be suitable nanocarriers for drugs, whilst N-trimethyl chitosan chloride (TMC) coating of nanoparticles has been reported to further enhance their cellular delivery efficacy; the combination of the two has not been previously investigated...
June 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28626480/development-of-dry-powder-inhaler-containing-tadalafil-loaded-plga-nanoparticles
#3
Jaleh Varshosaz, Somayeh Taymouri, Hamed Hamishehkar, Razieh Vatankhah, Shadi Yaghubi
Inhalable dry powders containing poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were developed for the delivery of tadalafil (TAD) for treatment of life-treating pulmonary arterial hypertension. Taguchi design was employed to evaluate the effects of different formulation variables on the physicochemical characteristics of PLGA-NPs prepared using emulsion solvent evaporation method. Inhalable PLGA-NPs of TAD were successfully prepared by co-spray drying the PLGA-NPs with inert carriers. Physicochemical characteristics and in vitro deposition of the aerosolized drug were also evaluated...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28621369/transport-of-nanoparticles-across-pulmonary-surfactant-monolayer-a-molecular-dynamics-study
#4
Yan Xu, Li Deng, Hao Ren, Xianren Zhang, Fang Huang, Tongtao Yue
Pulmonary nanodrug delivery is an emerging concept, especially for targeted lung cancer therapy. Once inhaled, the nanoparticles (NPs) acting as drug carriers need to efficiently cross the pulmonary surfactant monolayer (PSM) of lung alveoli, which act as the first barrier for external particles entering the lung. Herein, by performing molecular dynamics simulations, we study how inhaled NPs interact with the PSM, particularly focusing on the transport of NPs with different properties across the PSM. While hydrophilic NPs translocate directly across the PSM, transport of hydrophobic NPs is achieved as the PSM wraps them...
June 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28619456/how-does-secondary-processing-affect-the-physicochemical-properties-of-inhalable-salbutamol-sulphate-particles-a-temporal-investigation
#5
Joana T Pinto, Snezana Radivojev, Sarah Zellnitz, Eva Roblegg, Amrit Paudel
As pulmonary drug delivery is extended from low doses to high doses, physicochemical characteristics of the active pharmaceutical ingredient gain importance in the development of dry powder inhalers. Therefore, the present work aims to understand the impact of distinct engineering techniques on the process induced physicochemical characteristics of salbutamol sulphate particles over time. The particle engineering techniques chosen were jet-milling and spray-drying, two well used processes in the production of predominately crystalline and amorphous inhalable particles, respectively...
June 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28599855/impact-of-droplet-evaporation-rate-on-resulting-in-vitro-performance-parameters-of-pressurized-metered-dose-inhalers
#6
Poonam Sheth, Matthew R Grimes, Stephen W Stein, Paul B Myrdal
Pressurized metered dose inhalers (pMDIs) are widely used for the treatment of pulmonary diseases. The overall efficiency of pMDI drug delivery may be defined by in vitro parameters such as the amount of drug that deposits on the model throat and the proportion of the emitted dose that has particles that are sufficiently small to deposit in the lung (i.e., fine particle fraction, FPF). The study presented examines product performance of ten solution pMDI formulations containing a variety of cosolvents with diverse chemical characteristics by cascade impaction with three inlets (USP induction port, Alberta Idealized Throat, and a large volume chamber)...
June 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28598050/consensus-document-on-home-nebulization-for-maintenance-treatment-of-obstructive-airway-diseases-a-joint-initiative-by-the-national-allergy-asthma-bronchitis-institute-naabi-and-chest-research-foundation-crf
#7
Aloke G Ghoshal, Sundeep Salvi, Raja Dhar, Randeep Guleria, Ashok Mahashur, Anshuman Mukhopadhyay, Rmpl Ramanathan
Recent years have seen an increase in the use of nebulizers for delivering maintenance therapy in obstructive airway diseases (OADs) such as asthma and chronic obstructive pulmonary disease (COPD). The probable factors associated with this increase at home are: convenience of drug delivery, technological advances making the nebulizer equipment more efficient and portable, increase in the prevalence of OADs and the ageing population which may impact the optimal use of handheld inhalers such as pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs)...
May 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28596137/reshaping-antibiotics-through-hydrophobic-drug-bile-acid-ionic-complexation-enhances-activity-against-staphylococcus-aureus-biofilms
#8
Stefano Giovagnoli, Donatella Pietrella, Lanfranco Barberini, Claudio Santi, Andrea Carotti, Alessandro di Michele, Maurizio Ricci
The antibiotic era is on the verge of a profound change and facing a ground shaking crisis. The frequent failures of antibiotic treatments are often associated with biofilm formation, which is responsible for chronic infections, exacerbation as well as reinfection. So far, albeit the large number of valuable strategies employed to combat biofilm formation, little success has been recorded. In this work, we propose a simple approach, based on hydrophobic ionic complexation with the bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), to enhance anti-biofilm activity of well-known antibiotics, namely kanamycin (K), amikacin (A) and vancomycin (V)...
June 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28584899/development-of-aerosol-phospholipid-microparticles-for-the-treatment-of-pulmonary-hypertension
#9
Sarah Brousseau, Zimeng Wang, Sweta K Gupta, Samantha A Meenach
Pulmonary arterial hypertension (PAH) is an incurable cardiovascular disease characterized by high blood pressure in the arteries leading from the heart to the lungs. Over two million people in the USA are diagnosed with PAH annually and the typical survival rate is only 3 years after diagnosis. Current treatments are insufficient because of limited bioavailability, toxicity, and costs associated with approved therapeutics. Aerosol delivery of drugs is an attractive approach to treat respiratory diseases because it increases localized drug concentration while reducing systemic side effects...
June 5, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28584212/variations-of-postresuscitation-lung-function-after-thrombolysis-therapy-in-a-cardiac-arrest-porcine-model-caused-by-pulmonary-thromboembolism
#10
Jun Yang, Lian-Xing Zhao, Chun-Sheng Li, Nan Tong, Hong-Li Xiao, Le An
BACKGROUND: Study of lung function in survivor from cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) was rare. The aim of this study was to investigate the variations of postresuscitation lung function after thrombolysis treatment in a CA porcine model caused by PTE. METHODS: After 2 min of untreated CA, pigs of 10-12 weeks with a weight of 30 ± 2 kg (n = 24) were treated with recombinant human tissue plasminogen activator (50 mg). Cardiopulmonary resuscitation (CPR) and ventilation were initiated after drug administration...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28574733/mechanistic-investigation-of-mixing-segregation-of-ordered-mixtures-experiments-numerical-simulations
#11
Saurabh Sarkar, Bruna Minatovicz, Kyrre Thalberg, Bodhisattwa Chaudhuri
Pulmonary delivery of cohesive and micronized drugs through Dry Powder Inhalers (DPIs) is traditionally achieved through the formation of ordered mixtures. In order to improve the mechanistic understanding of formation of ordered mixtures, the system consisting of micronized lactose (AZFL, representative of an active pharmaceutical ingredient) and a coarse particle carrier (LH100) is investigated as a function of different process and material variables in a high shear mixer (HSM) and in a low shear double cone (DCN) blender, using both experimental and numerical methods...
June 2, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28574335/toxicity-of-orally-inhaled-drug-formulations-at-the-alveolar-barrier-parameters-for-initial-biological-screening
#12
Eleonore Fröhlich
Oral delivery is the most common mode of systemic drug application. Inhalation is mainly used for local therapy of lung diseases but may also be a promising route for systemic delivery of drugs that have poor oral bioavailability. The thin alveolar barrier enables fast and efficient uptake of many molecules and could deliver small molecules and proteins, which are susceptible to degradation and show poor absorption by oral application. The low rate of biotransformation and proteolytic degradation increases bioavailability of drugs but accumulation of not absorbed material may impair normal lung function...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28559256/aerosolized-polymyxin-b-for-treatment-of-respiratory-tract-infections-determination-of-pharmacokinetic-pharmacodynamic-indices-for-aerosolized-polymyxin-b-against-pseudomonas-aeruginosa-in-a-mouse-lung-infection-model
#13
Yu-Wei Lin, Qi Tony Zhou, Nikolas J Onufrak, Veronika Wirth, Ke Chen, Jiping Wang, Alan Forrest, Hak-Kim Chan, Jian Li
Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD) and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were conducted in neutropenic infected mice and the data were analyzed by a population PK model...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#14
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28546371/pediatric-aerosol-therapy
#15
Ariel Berlinski
Inhaled medications are the mainstay of therapy for many pediatric pulmonary diseases. Device and delivery technique selection is key to improving lung deposition of inhaled drugs. This paper will review the subject in relationship to several pediatric clinical situations: acute pediatric asthma, transnasal aerosol delivery, delivery through tracheostomies, and delivery during noninvasive and invasive mechanical ventilation. This review will focus on the pediatric age group and will not include neonates.
June 2017: Respiratory Care
https://www.readbyqxmd.com/read/28541666/unveiling-the-molecular-structure-of-pulmonary-surfactant-corona-on-nanoparticles
#16
Qinglin Hu, Xuan Bai, Guoqing Hu, Yi Y Zuo
The growing risk of human exposure to airborne nanoparticles (NPs) causes a general concern on the biosafety of nanotechnology. Inhaled NPs can deposit in the deep lung at which they interact with the pulmonary surfactant (PS). Despite the increasing study of nano-bio interactions, detailed molecular mechanisms by which inhaled NPs interact with the natural PS system remain unclear. Using coarse-grained molecular dynamics simulation, we studied the interaction between NPs and the PS system in the alveolar fluid...
May 31, 2017: ACS Nano
https://www.readbyqxmd.com/read/28536654/recent-advances-in-capsule-based-dry-powder-inhaler-technology
#17
REVIEW
Federico Lavorini, Massimo Pistolesi, Omar S Usmani
Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28522424/cyclodextrin-based-nanocarriers-containing-a-synergic-drug-combination-a-potential-formulation-for-pulmonary-administration-of-antitubercular-drugs
#18
Giuseppina Salzano, Jitendra Wankar, Stefano Ottani, Baptiste Villemagne, Alain R Baulard, Nicolas Willand, Priscille Brodin, Ilse Manet, Ruxandra Gref
Tuberculosis (TB) remains a major global health problem. The use of ethionamide (ETH), a main second line drug, is associated to severe toxic side-effects due to its low therapeutic index. In this challenging context, "booster" molecules have been synthetized to increase the efficacy of ETH. However, the administration of ETH/booster pair is mostly hampered by the low solubility of these drugs and the tendency of ETH to crystallize. Here, ETH and a poorly water-soluble booster, so-called BDM43266, were simultaneously loaded in polymeric β-cyclodextrin nanoparticles (pβCyD NPs) following a "green" protocol...
May 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28510480/dry-powder-inhaler-formulation-of-rifampicin-an-improved-targeted-delivery-system-for-alveolar-tuberculosis
#19
Tejal Rawal, Laurent Kremer, Iman Halloum, Shital Butani
BACKGROUND: The delivery of antitubercular drugs through direct lung targeting can lead to reduction in the dose as well as side effects of the drug. In the present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin was prepared to achieve direct targeting of the drug into the lungs. METHODS: The dry powder inhaler formulation was prepared by simply mixing micronized rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug were prepared with various lactose grades (Inhalac(®), Respitose,(®) and Lactohale(®))...
May 16, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28507469/lungs-deposition-and-pharmacokinetic-study-of-submicron-budesonide-particles-in-wistar-rats-intended-for-immediate-effect-in-asthma
#20
Abdul Rauf, Aseem Bhatnagar, S S Sisodia, Roop K Khar, Farhan J Ahmad
The purpose of the present investigation was to study the aerosolization, lungs deposition and pharmacokinetic study of inhalable submicron particles of budesonide in male Wistar rats. Submicron particles were prepared by antisolvent nanoprecipitation method and freeze-dried to obtain free flowing powder. The freeze-drying process yielded dry powder with desirable aerodynamic properties for inhalation therapy. An in-house model inhaler was designed to deliver medicine to lungs, optimized at dose level of 10 mg for 30 sec of fluidization...
2017: EXCLI journal
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